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Vaccine . Protective efficacy of the UniFluVec influenza vaccine vector against the highly pathogenic influenza A/Indonesia/5/2005 (H5N1) strain in

tetano

Editor, Senior Moderator
Vaccine


. 2025 Oct 4:65:127795.
doi: 10.1016/j.vaccine.2025.127795. Online ahead of print. Protective efficacy of the UniFluVec influenza vaccine vector against the highly pathogenic influenza A/Indonesia/5/2005 (H5N1) strain in ferrets

Julia Romanova[SUP] 1 [/SUP], Artem Krokhin[SUP] 2 [/SUP], Boris Ferko[SUP] 3 [/SUP], Dirk Pleimes[SUP] 4 [/SUP], Eva Vareckova[SUP] 5 [/SUP], Frantisek Kostolansky[SUP] 6 [/SUP], Andrej Egorov[SUP] 7 [/SUP]



Affiliations
Free article Abstract

Background: The emergence of new influenza strains with unpredictable antigenic properties poses a significant vaccination challenge. The increasing incidence of human H5 infections underscores the urgent need for effective pre-pandemic vaccines.
Methods: The UniFluVec and UniFluVec-wtNS1 viruses were designed as H1N1pdm vaccine candidates. Both viruses contained a heterologous A/Singapore/1/57-like (H2N2) NEP gene, which served as an attenuation factor. UniFluVec additionally carried a truncated to 124 amino acids NS1 gene, and an insertion of conserved influenza sequences. UniFluVec-wtNS1 retained the wild-type NS1 gene. The impact of NS1 and NEP modifications on attenuation and phenotypic markers was assessed in cells and mice. Safety and prophylactic efficacy were assessed in ferrets following a single intranasal immunisation with the maximum feasible dose (8.7 log[SUB]10[/SUB] EID[SUB]50[/SUB]), followed by challenge with the highly pathogenic avian influenza virus (HPAIV) A/Indonesia/5/2005 (H5N1).
Results: Modifications in NS1 and NEP independently and synergistically induced a temperature-sensitive phenotype and enhanced type I/II interferon response, resulting in a highly attenuated vaccine profile. UniFluVec, incorporating both modifications within the NS genomic segment, demonstrated superior viral clearance, reducing lung damage, and ensuring 100 % survival in infected animals.
Conclusion: The replication-deficient UniFluVec vector demonstrates safety, immunogenicity, and protective efficacy against the heterologous HPAIV strain in ferrets following a single intranasal administration.

Keywords: Avian influenza; Challenge model; Ferrets; Live influenza vaccine; Replication-deficient virus; UniFluVec vector.

 
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